Subcutaneous IVIG?

abstract & commentary

Synopsis: The term intravenous immune globulin (IVIG) has become a misnomer. IVIG was safely and effectively administered to eight patients; this route is believed to be associated with reduced adverse effects, but the total volume that can be given is limited.

Source: Stiehm ER, et al. Slow subcutaneous human intravenous immunoglobulin in the treatment of antibody immunodeficiency: Use of an old method with a new product. J Allergy Clin Immunol 1998;101:848-849.

Stiehm and colleagues describe eight patients that received 10% intravenous immune globulin (IVIG) via the subcutaneous route. Subcutaneous infusions of immune globulin were given weekly or biweekly using a battery-operated pump and a 20 mL syringe connected via tubing to a 1 cm × 24 gauge needle. The usual site of infusion was the abdominal wall 2 inches from the umbilicus. The site was rotated 90° at each visit and the typical infusion time was three hours. Usual doses given were 100 mg/kg/wk, although doses as high as 250 mg/kg were given every three weeks via this method.

In all patients, the subcutaneous route was chosen because of problems when IVIG was administered by the intravenous route. Four of the patients had poor venous access, two had prior anaphylactic reactions, one experienced severe aseptic meningitis, and another had rapid immunoglobulin catabolism. Three different brands of IVIG were used with comparable efficacy, lower side effects, and more consistent and sustained blood levels. While the concentration area under the curve after subcutaneous IVIG is equivalent to that when given intravenously, the peak level does not occur until four days later. This slow release of immunoglobulin into the blood stream is felt to be responsible for decreased side effects and more consistent blood levels, especially in patients with rapid immunoglobulin catabolism. To alleviate symptoms in some patients, they were premedicated with aspirin, acetaminophen, oral diphenhydramine, or intravenous hydrocortisone prior to infusions.

Comment by Thomas g. Schleis, MS, RPh

Infectious disease specialists are often referred patients with chronic sinusitis or pulmonary infections who are found to have compromised immune systems. Often, the response of these patients to immune globulin therapy is dramatic, with a significant decrease in infection rate. Although the subcutaneous infusion of IVIG is not new,1-4 I became aware of this method of administration at an immunology meeting. Most immunologists I spoke with feel this will be the preferred method of administration of IVIG in the future.

There are limitations to this method of adminstration, however. Infusions must be given more frequently—often weekly. This may present a problem for some patients, especially those who are used to receiving infusions on a monthly basis. It is also only suitable for relatively small volumes, such as 100-150 mL, making it unsuitable for treatment of certain autoimmune disorders, ITP, or other diseases where high doses are used. Nonetheless, for those patients experiencing significant side effects to immune globulin via the intravenous route, it does provide a potentially effective alternative. In the past, we have had several patients who experienced severe aseptic meningitis after IVIG infusions, despite decreasing the infusion rate in half and pretreatment with steroids and analgesics. These patients would certainly be candidates for subcutaneous therapy.

Another option may be a slow (24-48 hour) intravenous infusion of IVIG using an ambulatory infusion pump. To my knowledge, this has not been studied in patients experiencing side effects at more conventional infusion rates. A slow intravenous infusion may mimic the slow release of immunoglobulins into the bloodstream, which is felt to be responsible for the decreased side effects with subcutaneous infusions. This method would have the advantage of not being limited by dosage or volume.

References

1. Berger M, et al. High-dose immunoglobulin replacement therapy by slow subcutaneous infusion during pregnancy. JAMA 1982;247:2824-2825.

2. Gardulf A, et al. Home treatment of hypogammaglobulinaemia with subcutanous gammaglobulin by rapid infusion. Lancet 1991;338:162-166.

3. Gardulf A, et al. The life situations of patients with primary antibody deficiency untreated or treated with subcutaneous gammaglobulin infusions. Clin Exp Immunol 1993;92:200-204.

4. Abrahamsen TG, et al. Home therapy with subcutaneous immunoglobulin infusions in children with congenital immunodeficiencies. Pediatrics 1996;98: 1127-1131.